Annals of Hematology

, Volume 93, Issue 1, pp 113–121 | Cite as

Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea—experience from 110 patients

  • Kihyun KimEmail author
  • Seok Jin Kim
  • Verena Voelter
  • Cheolwon Suh
  • Sung-Soo Yoon
  • Je-Jung Lee
  • Jae-Yong Kwak
  • Hun-Mo Ryoo
  • Yang Soo Kim
  • Joon Ho Moon
  • Seong Kyu Park
  • Sung-Hyun Kim
  • Yeung-Chul Mun
  • Jin Seok Kim
  • Hyeon-Seok Eom
  • Deog-Yeon Jo
  • Hyun Jung Jun
  • Ki-Hwan Kim
  • Jeong-Ok Lee
  • Jae Hoon Lee
  • Chang-Ki MinEmail author
  • Korean Multiple Myeloma Working Party (KMMWP)
Original Article


We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.


Lenalidomide Relapsed myeloma Korean 



KK, SJK, VV, CS, S-SY, J-JL, J-YK, H-MR, YSK, JHM, SKP, S-HK, Y-CM, JSK, H-SE, D-YJ, HJJ, K-HK, J-OL, JHK, and C-KM performed the research; KK, S-SY, and C-KM designed the research; CS, C-KM, and J-JL contributed essential reagents or tools; KK analyzed the data; and KK, SJK, and VV wrote the paper.

Conflict of interest

VV is an employee of Celgene Corporation. The other writers have no conflicts of interests.


  1. 1.
    Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, Prince HM (2010) Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 24(1):22–32. doi: 10.1038/leu.2009.236 PubMedCrossRefGoogle Scholar
  2. 2.
    Zhu YX, Kortuem KM, Stewart AK (2013) Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma 54(4):683–687. doi: 10.3109/10428194.2012.728597 PubMedCrossRefGoogle Scholar
  3. 3.
    Gandhi AK, Kang J, Capone L, Parton A, Wu L, Zhang LH, Mendy D, Lopez-Girona A, Tran T, Sapinoso L, Fang W, Xu S, Hampton G, Bartlett JB, Schafer P (2010) Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 10(2):155–167PubMedCrossRefGoogle Scholar
  4. 4.
    Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC (2006) A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108(10):3458–3464. doi: 10.1182/blood-2006-04-015909 PubMedCrossRefGoogle Scholar
  5. 5.
    Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357(21):2123–2132. doi: 10.1056/NEJMoa070594 PubMedCrossRefGoogle Scholar
  6. 6.
    Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357(21):2133–2142. doi: 10.1056/NEJMoa070596 PubMedCrossRefGoogle Scholar
  7. 7.
    Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, Rajkumar SV, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2008) Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 112(12):4445–4451. doi: 10.1182/blood-2008-02-141614 PubMedCrossRefGoogle Scholar
  8. 8.
    Stadtmauer EA, Weber DM, Niesvizky R, Belch A, Prince MH, San Miguel JF, Facon T, Olesnyckyj M, Yu Z, Zeldis JB, Knight RD, Dimopoulos MA (2009) Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma. Eur J Haematol 82(6):426–432. doi: 10.1111/j.1600-0609.2009.01257.x PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Harousseau JL, Dimopoulos MA, Wang M, Corso A, Chen C, Attal M, Spencer A, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2010) Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica 95(10):1738–1744. doi: 10.3324/haematol.2009.015917 PubMedCrossRefGoogle Scholar
  10. 10.
    Chanan-Khan AA, Lonial S, Weber D, Borrello I, Foa R, Hellmann A, Dimopoulos M, Swern AS, Knight R (2012) Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients >/=65 years old with relapsed or refractory multiple myeloma. Int J Hematol. doi: 10.1007/s12185-012-1125-7 PubMedCentralPubMedGoogle Scholar
  11. 11.
    Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2009) Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23(11):2147–2152. doi: 10.1038/leu.2009.147 PubMedCrossRefGoogle Scholar
  12. 12.
    Iida S, Chou T, Okamoto S, Nagai H, Hatake K, Murakami H, Takagi T, Shimizu K, Lau H, Takeshita K, Takatoku M, Hotta T (2010) Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol 92(1):118–126. doi: 10.1007/s12185-010-0624-7 PubMedCrossRefGoogle Scholar
  13. 13.
    Hou J, Du X, Jin J, Cai Z, Chen F, Zhou DB, Yu L, Ke X, Li X, Wu D, Meng F, Ai H, Zhang J, Wortman-Vayn H, Chen N, Mei J, Wang J (2013) A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. J Hematol Oncol 6(1):41. doi: 10.1186/1756-8722-6-41 PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV (2006) International uniform response criteria for multiple myeloma. Leukemia 20(9):1467–1473. doi: 10.1038/sj.leu.2404284 PubMedCrossRefGoogle Scholar
  15. 15.
    Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D, Jagannath S, Facon T, Avet-Loiseau H, Lonial S, Palumbo A, Zonder J, Ludwig H, Vesole D, Sezer O, Munshi NC, San Miguel J (2011) Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 117(18):4691–4695. doi: 10.1182/blood-2010-10-299487 PubMedCrossRefGoogle Scholar
  16. 16.
    Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11(1):29–37. doi: 10.1016/S1470-2045(09)70284-0 PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Dimopoulos MA, Palumbo A, Attal M, Beksac M, Davies FE, Delforge M, Einsele H, Hajek R, Harousseau JL, da Costa FL, Ludwig H, Mellqvist UH, Morgan GJ, San-Miguel JF, Zweegman S, Sonneveld P (2011) Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia 25(5):749–760. doi: 10.1038/leu.2011.3 PubMedCrossRefGoogle Scholar
  18. 18.
    Larson D, Kyle RA, Rajkumar SV (2012) Prevalence and monitoring of oligosecretory myeloma. N Engl J Med 367(6):580–581. doi: 10.1056/NEJMc1206740 PubMedCrossRefGoogle Scholar
  19. 19.
    Alegre A, Oriol-Rocafiguera A, Garcia-Larana J, Mateos MV, Sureda A, Martinez-Chamorro C, Cibeira MT, Aguado B, Knight R, Rosettani B (2012) Efficacy, safety and quality-of-life associated with lenalidomide plus dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience. Leuk Lymphoma 53(9):1714–1721. doi: 10.3109/10428194.2012.662643 PubMedCrossRefGoogle Scholar
  20. 20.
    Alegre A, Aguado B, Giraldo P, Rios E, Canovas A, Ibanez A, Castillo I, Hernandez MT, Oriol A, Palomera L, Rodriguez JN, Garcia FL, Calvo JM, Martinez-Chamorro C, de la Serna J, Lahuerta JJ (2011) Lenalidomide is effective as salvage therapy in refractory or relapsed multiple myeloma: analysis of the Spanish Compassionate Use Registry in advanced patients. Int J Hematol 93(3):351–360. doi: 10.1007/s12185-011-0785-z PubMedCrossRefGoogle Scholar
  21. 21.
    Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C, Garderet L, Belhadj K, Dorvaux V, Minvielle S, Moreau P (2010) Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia 24(3):623–628. doi: 10.1038/leu.2009.273 PubMedCrossRefGoogle Scholar
  22. 22.
    DU X, JIN J, CAI Z, CHEN F, ZHOU DB, YU L, KE X, LI X, WU D, MENG F, AI H, WANG J, ZHANG J, MEI J, HOU J (2013) Efficacy and safety of lenalidomide 25 mg + low-dose dexamethasone in Chinese patients with relapsed/refractory myeloma. Clin Lymphoma Myeloma Leuk 13(s1):s145Google Scholar
  23. 23.
    Guglielmelli T, Bringhen S, Rrodhe S, Gay F, Cavallo F, Berruti A, Montefusco V, Piro E, Benevolo G, Petrucci MT, Caravita T, Offidani M, Corradini P, Boccadoro M, Saglio G, Palumbo A (2011) Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients. Eur J Cancer 47(6):814–818. doi: 10.1016/j.ejca.2010.12.026 PubMedCrossRefGoogle Scholar
  24. 24.
    Carrier M, Le Gal G, Tay J, Wu C, Lee AY (2011) Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 9(4):653–663. doi: 10.1111/j.1538-7836.2011.04215.x PubMedCrossRefGoogle Scholar
  25. 25.
    Menon SP, Rajkumar SV, Lacy M, Falco P, Palumbo A (2008) Thromboembolic events with lenalidomide-based therapy for multiple myeloma. Cancer 112(7):1522–1528. doi: 10.1002/cncr.23336 PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Niesvizky R, Martinez-Banos D, Jalbrzikowski J, Christos P, Furst J, De Sancho M, Mark T, Pearse R, Mazumdar M, Zafar F, Pekle K, Leonard J, Jayabalan D, Coleman M (2007) Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma. Leuk Lymphoma 48(12):2330–2337. doi: 10.1080/10428190701647887 PubMedCrossRefGoogle Scholar
  27. 27.
    Koh Y, Bang SM, Lee JH, Yoon HJ, Do YR, Ryoo HM, Lee N, Kim SJ, Kim K, Yoon SS, Won JH, Mun YC, Lee MH, Rhee KH, Kim HJ, Eom H, Kim MK, Shin HC (2010) Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide. Ann Hematol 89(2):201–206. doi: 10.1007/s00277-009-0807-6 PubMedCrossRefGoogle Scholar
  28. 28.
    Wu SY, Yeh YM, Chen YP, Su WC, Chen TY (2012) Low incidence of thromboembolism in relapsed/refractory myeloma patients treated with thalidomide without thromboprophylaxis in Taiwan. Ann Hematol 91(11):1773–1778. doi: 10.1007/s00277-012-1506-2 PubMedCrossRefGoogle Scholar
  29. 29.
    Touzeau C, Blin N, Clavert A, Roland V, Loirat M, Tessoulin B, Le Gouill S, Planche L, Pennetier M, Mahe B, Mohty M, Malard F, Peterlin P, Dubruille V, Moreau P (2012) Efficacy of lenalidomide plus dexamethasone in patients older than 75 years with relapsed multiple myeloma. Leuk Lymphoma 53(7):1318–1320. doi: 10.3109/10428194.2011.654116 PubMedCrossRefGoogle Scholar
  30. 30.
    Klein U, Jauch A, Hielscher T, Hillengass J, Raab MS, Seckinger A, Hose D, Ho AD, Goldschmidt H, Neben K (2011) Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer 117(10):2136–2144. doi: 10.1002/cncr.25775 PubMedCrossRefGoogle Scholar
  31. 31.
    Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M, Iakovaki M, Matsouka C, Mparmparoussi D, Roussou M, Efstathiou E, Terpos E (2010) Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia 24(10):1769–1778. doi: 10.1038/leu.2010.175 PubMedCrossRefGoogle Scholar
  32. 32.
    Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, Mansoor A, Chen C, Masih-Khan E, Trieu Y, Bruyere H, Stewart DA, Bahlis NJ (2009) Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood 114(3):522–525. doi: 10.1182/blood-2008-12-193458 PubMedCrossRefGoogle Scholar
  33. 33.
    Dimopoulos M, Alegre A, Stadtmauer EA, Goldschmidt H, Zonder JA, de Castro CM, Masliak Z, Reece D, Olesnyckyj M, Yu Z, Weber DM (2010) The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function. Cancer 116(16):3807–3814. doi: 10.1002/cncr.25139 PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Kleber M, Ihorst G, Udi J, Koch B, Wasch R, Engelhardt M (2012) Prognostic risk factor evaluation in patients with relapsed or refractory multiple myeloma receiving lenalidomide treatment: analysis of renal function by eGFR and of additional comorbidities by comorbidity appraisal. Clin Lymphoma Myeloma Leuk 12(1):38–48. doi: 10.1016/j.clml.2011.09.216 PubMedCrossRefGoogle Scholar
  35. 35.
    Oehrlein K, Langer C, Sturm I, Ponisch W, Hahn-Ast C, Kuhn S, Weisel KC (2012) Successful treatment of patients with multiple myeloma and impaired renal function with lenalidomide: results of 4 German Centers. Clin Lymphoma Myeloma Leuk 12(3):191–196. doi: 10.1016/j.clml.2012.01.001 PubMedCrossRefGoogle Scholar
  36. 36.
    Dimopoulos MA, Christoulas D, Roussou M, Kastritis E, Migkou M, Gavriatopoulou M, Matsouka C, Mparmparoussi D, Psimenou E, Grapsa I, Efstathiou E, Terpos E (2010) Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment. Eur J Haematol 85(1):1–5. doi: 10.1111/j.1600-0609.2010.01432.x PubMedGoogle Scholar
  37. 37.
    Dimopoulos MA, Richardson PG, Brandenburg N, Yu Z, Weber DM, Niesvizky R, Morgan GJ (2012) A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 119(12):2764–2767. doi: 10.1182/blood-2011-08-373514 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Kihyun Kim
    • 1
    Email author
  • Seok Jin Kim
    • 1
  • Verena Voelter
    • 2
  • Cheolwon Suh
    • 3
  • Sung-Soo Yoon
    • 4
  • Je-Jung Lee
    • 5
  • Jae-Yong Kwak
    • 6
  • Hun-Mo Ryoo
    • 7
  • Yang Soo Kim
    • 8
  • Joon Ho Moon
    • 9
  • Seong Kyu Park
    • 10
  • Sung-Hyun Kim
    • 11
  • Yeung-Chul Mun
    • 12
  • Jin Seok Kim
    • 13
  • Hyeon-Seok Eom
    • 14
  • Deog-Yeon Jo
    • 15
  • Hyun Jung Jun
    • 16
  • Ki-Hwan Kim
    • 17
  • Jeong-Ok Lee
    • 18
  • Jae Hoon Lee
    • 19
  • Chang-Ki Min
    • 20
    Email author
  • Korean Multiple Myeloma Working Party (KMMWP)
  1. 1.Division of Hematology-Oncology, Department of MedicineSamsung Medical Center, Sungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Celgene KoreaSeoulSouth Korea
  3. 3.Department of OncologyAsan Medical Center, University of Ulsan College of MedicineSeoulSouth Korea
  4. 4.Department of Internal MedicineSeoul National University HospitalSeoulSouth Korea
  5. 5.Department of Hematology-OncologyChonnam National University Hwasun HospitalHwasunSouth Korea
  6. 6.Department of Internal MedicineChonbuk National University Medical SchoolJeonjuSouth Korea
  7. 7.Department of Internal MedicineDaegu Catholic University Medical CenterDaeguSouth Korea
  8. 8.Department of Internal MedicineKosin University Gospel HospitalBusanSouth Korea
  9. 9.Department of Internal MedicineKyungpook National University HospitalDaeguSouth Korea
  10. 10.Department of Internal medicineSoonchunhyang University Bucheon HospitalBucheonSouth Korea
  11. 11.Department of Internal MedicineDong-A University College of MedicineBusanSouth Korea
  12. 12.Department of Internal MedicineEwha Womans University School of MedicineSeoulSouth Korea
  13. 13.Division of Hematology, Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea
  14. 14.Hematology-Oncology Clinic, National Cancer CenterGoyang-siSouth Korea
  15. 15.Department of Internal MedicineChungnam National University Hospital, Chungnam National University College of MedicineDaejeonSouth Korea
  16. 16.Medical Oncology and Hematology, Department of Internal MedicineSeoul Medical CenterSeoulSouth Korea
  17. 17.Department of Internal MedicineSeoul National University Boramae HospitalSeoulSouth Korea
  18. 18.Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
  19. 19.Department of Internal MedicineGachon University Gil HospitalIncheonSouth Korea
  20. 20.Division of Hematology, Department of Internal MedicineSeoul St. Mary’s Hospital, The Catholic University of KoreaSeoulSouth Korea

Personalised recommendations